Plasma autoantibody associated with basal-like breast cancer-GST4 Array

Background: Basal-like breast cancer (BLBC) is a rare aggressive subtype that is less likely to be detected through mammographic screening. Identification of circulating markers associated with BLBC could have promise in detection and management of this deadly disease. Methods: Using samples from the Polish Breast Cancer study, a high-quality population-based case-control study of breast cancer, we screened 10,000 antigens on protein arrays using 45 BLBC patients and 45 controls, and identified 748 promising plasma autoantibodies (AAbs) associated with BLBC. ELISA assays of promising markers were performed on a total of 145 BLBC cases and 145 age-matched controls. Sensitivities at 98% specificity were calculated and a BLBC classifier was constructed. Results: We identified a 13-AAbs (CTAG1B, CTAG2, TP53, RNF216, PPHLN1, PIP4K2C, ZBTB16, TAS2R8, WBP2NL, DOK2, PSRC1, MN1, TRIM21) that distinguished BLBC from controls with 33% sensitivity and 98% specificity. We also discovered a strong association of TP53 AAb with its protein expression (p=0.009) in BLBC patients. Conclusions: These AAbs warrant further investigation in clinical studies to determine their value for further understanding the biology of BLBC and possible detection. The immunoreactivity was compared between 45 BLBC cases and 45 controls against 10,000 human proteins that printed on microscopic slides

背景：基底样乳腺癌（Basal-like breast cancer, BLBC）是一种罕见且侵袭性强的亚型，且更难通过乳腺钼靶筛查检出。识别与基底样乳腺癌相关的循环标志物，有望为这种致命疾病的检测与管理提供新的思路。
方法：本研究依托一项高质量的乳腺癌人群为基础病例对照研究——波兰乳腺癌研究的样本，利用45例基底样乳腺癌患者与45例对照的样本，在蛋白质芯片上对10000种抗原进行筛选，最终识别出748种与基底样乳腺癌相关的潜在血浆自身抗体（autoantibodies, AAbs）。随后，针对筛选出的潜在标志物，在总计145例基底样乳腺癌病例与145例年龄匹配对照中开展酶联免疫吸附测定（enzyme-linked immunosorbent assay, ELISA）。计算了98%特异性下的灵敏度，并构建了基底样乳腺癌分类器。
结果：本研究识别出由13种自身抗体组成的标志物组合（CTAG1B、CTAG2、TP53、RNF216、PPHLN1、PIP4K2C、ZBTB16、TAS2R8、WBP2NL、DOK2、PSRC1、MN1、TRIM21），该组合可区分基底样乳腺癌与对照，灵敏度为33%，特异性达98%。此外，本研究还发现，基底样乳腺癌患者体内的TP53自身抗体与其蛋白表达水平存在显著关联（p=0.009）。
结论：上述自身抗体值得在临床研究中开展进一步探索，以明确其在深入解析基底样乳腺癌生物学特性以及潜在临床检测中的应用价值。本研究还针对印于显微玻片上的10000种人类蛋白，比较了45例基底样乳腺癌病例与45例对照的免疫反应性。